Effect of Cisplatin-Induced Acute Renal Failure on Bioavailability and Intestinal Secretion of Quinolone Antibacterial Drugs in Rats

Hiroaki Yamaguchi, Ikuko Yano, Hideyuki Saito, Ken Ichi Inui

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Purpose. The aim of this study was to clarify the effects of renal failure on intestinal secretion of quinolone antibacterial drugs. Methods. Pharmacokinetics of grepafloxacin, levofloxacin, and ciprofloxacin in cisplatin-induced acute renal failure (ARF) rats were evaluated, and intestinal and biliary clearance studies were examined. Transport experiments using culture cells were performed. Results. The bioavailability of grepafloxacin in ARF rats was 1.2-fold higher than that in normal rats. On the other hand, the bioavailability of ciprofloxacin in ARF rats was markedly decreased to half of that in normal rats, and that of levofloxacin was not changed. Intestinal clearance of grepafloxacin in ARF rats was 75% of that in normal rats, whereas that of ciprofloxacin was 1.4-fold higher than in normal rats, and that of levofloxacin was comparable between normal and ARF rats. Transport experiments using P-glycoprotein-expressing LLC-GA5-COL150 cells and human intestinal Caco-2 cells suggested that grepafloxacin and levofloxacin were substrates of P-glycoprotein and that ciprofloxacin was not, and that intestinal secretion of ciprofloxacin was mediated by a specific transport system distinct from organic cation and anion transporters and multidrug resistance-associated protein 2. Conclusions. Cisplatin-induced ARF differentially modulated the bioavailability and intestinal secretion of quinolones in rats.

Original languageEnglish
Pages (from-to)330-338
Number of pages9
JournalPharmaceutical research
Volume21
Issue number2
DOIs
Publication statusPublished - 2004 Feb 1

Keywords

  • Acute renal failure
  • Intestinal secretion
  • P-glycoprotein
  • Quinolones
  • Transport

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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